Over many years we have taken advantage of the special metabolism of
cancer cells involving an increased consumption of
glucose associated with
lactic acid production even in the presence of
oxygen, a phenomenon referred to as the "Warburg effect", to counteract
cancer cell growth. We have tested
3-bromopyruvate (3-BrPA), an inhibitor of
pyruvate-associated reactions. Firstly, we tested this agent, in vitro, in two
mesothelioma cell lines. Cellular response would appear to depend on the mode of administration (immediately or 24 h after seeding). Depending on the line, 3-BrPA induced a
cytostatic or cytotoxic effect. This effect was accompanied by cell death induction even in cells highly refractory to
cisplatin. Mitochondrial apoptotic death appeared to involve both lines; however, a different death pathway such as
necrosis cannot be excluded. Interestingly, 3-BrPA leads to a diminution of the expression of the anti-apotptoic
protein Mcl-1. We then tested 3-BrPA in vivo. Survival of nude mice bearing human
mesothelioma was significantly prolonged (p < 0.0001). Toxicity and clinical studies should be performed to test 3- BrPA as local
therapy for patients suffering from pleural or peritoneal
mesothelioma. Association with
cisplatin should be particularly considered.